Disruption of acvrl1 Increases Endothelial Cell Number in Zebrafish Cranial Vessels

Development. 2002 Jun;129(12):3009-19.

Abstract

The zebrafish mutant violet beauregarde (vbg) can be identified at two days post-fertilization by an abnormal circulation pattern in which most blood cells flow through a limited number of dilated cranial vessels and fail to perfuse the trunk and tail. This phenotype cannot be explained by caudal vessel abnormalities or by a defect in cranial vessel patterning, but instead stems from an increase in endothelial cell number in specific cranial vessels. We show that vbg encodes activin receptor-like kinase 1 (Acvrl1; also known as Alk1), a TGFbeta type I receptor that is expressed predominantly in the endothelium of the vessels that become dilated in vbg mutants. Thus, vbg provides a model for the human autosomal dominant disorder, hereditary hemorrhagic telangiectasia type 2, in which disruption of ACVRL1 causes vessel malformations that may result in hemorrhage or stroke. Movies available on-line

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Activin Receptors / genetics*
  • Activin Receptors / metabolism*
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Blood Vessels / abnormalities
  • Blood Vessels / embryology*
  • Cerebrovascular Circulation
  • Chromosome Mapping
  • DNA-Binding Proteins / metabolism
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental
  • Head / blood supply*
  • Head / embryology
  • Humans
  • Molecular Sequence Data
  • Mutation
  • Phosphoproteins / metabolism
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Smad Proteins
  • Smad5 Protein
  • Smad8 Protein
  • Telangiectasia, Hereditary Hemorrhagic / genetics
  • Telangiectasia, Hereditary Hemorrhagic / physiopathology
  • Trans-Activators / metabolism
  • Zebrafish / embryology
  • Zebrafish / genetics*
  • Zebrafish Proteins / genetics*
  • Zebrafish Proteins / metabolism*

Substances

  • DNA-Binding Proteins
  • Phosphoproteins
  • SMAD8 protein, human
  • Smad Proteins
  • Smad5 Protein
  • Smad8 Protein
  • Trans-Activators
  • Zebrafish Proteins
  • smad5 protein, zebrafish
  • Acvrl1 protein, zebrafish
  • Activin Receptors

Associated data

  • GENBANK/AF435024
  • GENBANK/AF435025